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Double hit key to successful immune attack on cancer and infection

Double hit key to successful immune attack on cancer and infection

Dr Axel Kallies has discovered how the production of
killer T cells is triggered during immune responses.

Walter and Eliza Hall Institute researchers have redefined how killer immune cells are mobilised in the body’s response to infections or cancer cells.

The discovery of how two pathways cooperate to unleash the immune system’s assassins, called cytotoxic or ‘killer’ T cells, could be harnessed in the future to improve the treatment of chronic infections or cancer.

Killer T cells detect, attack and kill abnormal cells in our body, such as cells that are infected with viruses or have undergone cancerous changes.

Dr Axel Kallies, Dr Annie Xin and Dr Frederick Masson investigated how killer T cells are generated during immune responses, in research published in this month’s edition of Nature Immunology.

The formation of killer T cells is guided by signals, called cytokines, released by other immune cells, Dr Kallies said. “These signals are transmitted to two separate regulator proteins within the T cell, called Blimp-1 and T-bet,” he said. “For several years it has been known that these molecules both contribute to the formation of killer T cells, but we haven’t understood how they work together.

“We showed that the combination of both signals triggers the formation of killer cells that can fight a viral infection. If one of these signals is lost, the immune response is dampened but still functional. This creates a buffered system that helps the organism to fight different types of infections or cancerous cells. It’s a great example of how our body has checks and balances in place to ensure the immune system is switched on at the right time – such as during an infection – but can be toned down at other times to avoid a damaging attack on healthy cells,” Dr Kallies said.

CD8 killer T cells are central to the recent breakthroughs in cancer immunotherapy, an extremely successful new approach to cancer treatment that harnesses the immune system to rid the body of cancer cells.

Dr Kallies said he hoped his research revealing how killer T cells are formed would lay the groundwork for future advances in cancer immunotherapy.

“There have been amazing improvements in immunotherapy recently that can be traced directly back to basic immunology research conducted over the last decade,” he said. “Our team is now looking at how we can apply our discoveries to approaches aimed at improving cancer therapies.”

The research was conducted while Dr Xin was a PhD student at the Walter and Eliza Hall Institute enrolled through The University of Melbourne’s Department of Medical Biology.

The research was supported by the National Health and Medical Research Council, the Australian Research Council, the Sylvia and Charles Viertel Foundation, the US National Institutes of Health, Howard Hughes Medical Institute, and the Victorian Government Operational Infrastructure Support Scheme.

The Walter and Eliza Hall Institute is the research powerhouse of the Victorian Comprehensive Cancer Centre, an alliance of leading Victorian hospitals and research centres committed to controlling cancer.